Anti-inflammatory composition

ABSTRACT

An anti-inflammatory composition is disclosed. The anti-inflammatory composition is be useful for a pharmaceutical composition or a cosmetic composition by not only having excellent stability on the skin and therefore being harmless to the human body, but also by controlling the expression of an inflammatory skin disease-related mediating factor and thereby exhibiting an excellent anti-inflammatory effect.

TECHNICAL FIELD

The present invention relates to an anti-inflammatory composition, andmore particularly, to an anti-inflammatory pharmaceutical compositionand an anti-inflammatory cosmetic composition having ananti-inflammatory effect by controlling an expression of an inflammatoryskin disease-related mediating factor.

BACKGROUND ART

Inflammation is one of the defense reactions of a living body to preventdamage to living tissue due to an increase of blood flow of an infectedarea, swelling, immune cells and antibody migration, pain, fever, andthe like, caused when histamine, kinin, and the like, are released bycell damage caused by external biologic causes (bacteria, viruses, andparasites), physiological causes (mechanical stimulation, heat,radiation, and electricity), chemical causes, and the like, thusresulting in vasodilation, an increase in capillary permeability, andaccumulation of macrophages at inflammatory sites.

An inflammatory skin disease generally refers to eczematous dermatitis.The eczema refers to a skin disease in which vesicles (small blisters)with itching, erythema (reddening of the skin), swelling, and the like,are seen in the acute phase, while lichniscation (indicating that linesof skin that are normally present on the skin such as palms becomeclearer due to dry and firm skin), scale, changes in skin color, and thelike, are seen while decreasing the swelling and the vesicle in thechronic phase. Examples of the eczematous dermatitis may include contactdermatitis, atopic dermatitis, and seborrheic dermatitis, and the like.

As described above, the inflammatory response in the skin starts as anaction to defend skin damage caused by physical stimulation, chemicalsubstances, bacteria, and the like, and various immune cells andinflammation-inducing cytokines are involved therein. Representativeexamples of the cytokine may include interleukin, a proliferationfactor, chemokine, a tumor necrosis factor, interferon, and the like.Specific examples of the cytokine may include insulin, insulin growthfactor (IGF)-I, IGF-II, epidermal growth factor (EGF), transforminggrowth factor (TGF)-α, TGF-β1, TGF-β2, fibroblast growth factor (FGF)-1,FGF-2, FGF-3, FGF-4, FGF-5, FGF-6, FGF-7, FGF-8, FGF-9, FGF-10, FGF-11,FGF-12, FGF-13, FGF-14, FGF-15, FGF-16, FGF-17, FGF-18, FGF-19, vascularendothelial growth factor (VEGF)-A, VEGF-B, VEGF-C, VEGF-D, nerve growthfactor (NGF), interleukin (IL)-1α, IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6,IL-7, IL-8, IL-9, IL-10, IL-11, IL-12, IL-13, IL-14, IL-15, IL-16,IL-17, IL-18, granulocyte macrophage colony stimulating factor (GM-CSF),granulocyte colony stimulating factor (G-CSF), macrophage colonystimulating factor (M-CSF), stem cell factor (SCF), flt-3 ligand (FL),angiopoietin, erythropoietin (EPO), thrombopoietin (TPO), oncostatin M(OSM), leukemia inhibitory factor (LIF), activin, inhibin, bonemorphogenetic protein (BMP), platelet-derived growth factor (PDGF),hepatocyte growth factor (HGF), tumor necrosis factor (TNF)-α, TNF-β,Fas ligand (Fas-L), CD40 ligand, macrophage inflammatory protein (MIP),monocyte chemoattractant protein (MCP), interferon (IFN)α, IFNβ, IFNγ,glial cell-derived neurotrophic factor (GDNF), angiotensin, and thelike.

Currently, synthetic medicines such as ibuprofen, antihistamines,steroids, cortisone, immunosuppressants, immune promoter, and the like,are used for prevention and treatment of inflammatory skin diseases.However, the treatment effect is temporary, there are many side effectssuch as simple symptom relief, hypersensitivity reaction, aggravation ofthe immune system, and the like, and there are limitations on thefundamental treatment of inflammation. In addition, Korean Patent No.0563548, Korean Patent No. 0697319, Korean Patent No. 1309172 and KoreanPatent No. 1141802 disclose various attempts to develop a cosmeticcomposition having an anti-inflammatory function using a naturalextract. However, the use amount of the composition is limited due toanother skin irritation, discoloration, or the like, or solubility inwater is not good, and thus it is difficult to obtain a substantialeffect due to limitation of application when the composition is appliedto an actual product.

Thus, the present applicant conducted intensive studies on degree ofactivity inhibition of inflammation-inducing cytokine which is aninflammatory skin disease-related mediating factor, and as a result,found that a compound derived from specific alcohol or amino acid is notonly safe on the skin because the compound has no cytotoxicity,allergenicity, and the like, but also because the compound effectivelyfunctions to inhibit production of inflammation-inducing cytokines(particularly, IL-8 and IL-17), and completed the present invention byproviding an anti-inflammatory composition including the same.

DISCLOSURE Technical Problem

An object of the present invention is to provide an anti-inflammatorycomposition capable of effectively inhibiting skin inflammation andhaving an excellent skin cell regeneration effect without causing skinside effects.

Technical Solution

In one general aspect, an anti-inflammatory composition includes: acompound represented by Chemical Formula 1 below as an activeingredient:

in Chemical Formula 1,

R₁ is hydrogen, (C1-C30)alkyl, (C2-C30)alkenyl, (C2-C30)alkynyl,(C1-C30)alkoxy, or hydroxy(C1-C30)alkyl;

R₂ is (C1-C30)alkyl, (C2-C30)alkenyl, (C2-C30)alkynyl, (C1-C30)alkoxy,or hydroxy(C1-C30)alkyl; and

R₃ is

or a substituted or unsubstituted amino acid group, wherein R₁₁ ishydroxy(C1-C30)alkyl.

The anti-inflammatory composition according to an embodiment of thepresent invention may include the above-described compound as an activeingredient to control cytokine and inhibit expression of an inflammationmediating molecule, thereby controlling stimulation and inflammation. Indetail, the anti-inflammatory composition according to the presentinvention has excellent inhibitory effects, particularly, oninflammation-inducing cytokines such as interleukin-8 (IL-8),interleukin-17 (IL-17), and the like.

In other words, the anti-inflammatory composition according to anembodiment of the present invention may increase distribution of aregulatory T cell (Treg) that inhibits an activity of inflammatory cellssuch as macrophages or neutrophils, thereby effectively inhibitingexpression of inflammation to exhibit an excellent anti-inflammatoryeffect.

The anti-inflammatory composition according to the present invention maybe formulated into a pharmaceutical composition or a cosmeticcomposition including the compound represented by Chemical Formula 1above as an active ingredient, and the composition has an excellenteffect in improving inflammatory skin diseases, particularly, atopicdermatitis and/or allergic dermatitis.

Advantageous Effects

According to the present invention, the regulation of cytokine may besuppressed to effectively prevent the inflammatory reaction, and thusexcellent anti-inflammatory effects on inflammatory skin diseases,particularly, atopic dermatitis, allergic dermatitis, and the like, maybe exhibited.

Further, the anti-inflammatory composition containing the activeingredient according to the present invention may be safely applied tocosmetic compositions and pharmaceutical compositions of variousformulations since the anti-inflammatory composition does not havecytotoxicity and skin side effects.

DESCRIPTION OF DRAWINGS

FIG. 1 shows an increase of IL-8 and IL-17A in an atopicdermatitis-induced skin model (AD) as compared with a general skinmodel, and shows immunohistochemical results in which IL-8 and IL-17Aexpression was reduced when the anti-inflammatory composition accordingto the present invention was administered to the atopicdermatitis-induced skin model, similar to that of the general skinmodel.

FIG. 2 is a graph showing quantification of the immunohistochemicalresults obtained in FIG. 1.

BEST MODE

Hereinafter, an anti-inflammatory composition according to the presentinvention is described. Unless otherwise defined, the technical termsand scientific terms used herein have meanings generally understood bythose skilled in the art to which the present invention pertains. Knownfunctions and constitutions that may obscure the gist of the presentinvention with unnecessary detail will be omitted.

The term “inflammation” used herein refers to a phenomenon that isknown, for a series of defensive purposes, to minimize a reaction andrestore a damaged area to an original state thereof when a cell ortissue is damaged by some cause, and is collectively referred to ascausing nerves, blood vessels, and lymph vessels responses, humoralresponses, and cellular responses, thus resulting in pain, swelling,redness, fever, and the like, to induce dysfunction. An inflammatoryskin disease caused by the inflammation may be at least one selectedfrom the group consisting of atopic dermatitis, psoriasis, contactdermatitis, eczematous dermatitis, actinic dermatitis, seborrheicdermatitis, dermatitis herpetiformis, lichen planus, lichen sclerosus,pyoderma gangrenosum, pemphigus, epidermolysis bullosa, systemicsclerosis, dermatomyositis, polymyositis, inflammatory muscle lesions,leprosy, or Sézary's syndrome, and may include allergic dermatitis suchas urticaria, insect allergies, food allergies, and drug allergies,which fall within the same category.

The terms “IL-8” and “IL-17” used herein are one example of aninflammation-inducing cytokine, and an expression thereof iscontinuously increased by an inflammatory reaction, and thus suppressionof the IL-8 and IL-17 is very important to relieve the inflammation.Here, the IL-17 in the present invention may be selected from IL-17A,IL-17B, IL-17C, IL-17D, IL-17E, IL-17F, and the like. Particularly, theanti-inflammatory composition according to the present inventionincreases distribution of T cells and is superior in inhibiting IL-17A.Thus, for the term “IL-17” used in the present invention, IL-17A ispreferred.

The term “application” used herein refers to contacting the compositionaccording to the present invention to the skin of a subject by anysuitable method, and has a purpose of absorbing the composition into theskin by the application.

The term “improvement” used herein refers to all actions that improvethe inflammatory state or change the inflammatory state beneficially bythe application of the composition according to the present invention.

As a result of conducting intensive studies on the degree of activityinhibition of inflammation-inducing cytokine which is an inflammatoryskin disease-related mediating factor, the present applicant found thatthe compound represented by Chemical Formula 1 below effectivelyinhibited production of interleukin-8 and interleukin-17A which areinflammation-inducing cytokines.

In other words, according to the present invention, it is possible toimplement an excellent anti-inflammatory effect by inhibiting productionof an inflammatory skin disease-related mediating factor.

in Chemical Formula 1,

R₁ is hydrogen, (C1-C30)alkyl, (C2-C30)alkenyl, (C2-C30)alkynyl,(C1-C30)alkoxy, or hydroxy(C1-C30)alkyl;

R₂ is (C1-C30)alkyl, (C2-C30)alkenyl, (C2-C30)alkynyl, (C1-C30)alkoxy,or hydroxy(C1-C30)alkyl; and

R₃ is

or a substituted or unsubstituted amino acid group, wherein R₁₁ ishydroxy(C1-C30)alkyl.

The terms “alkyl”, “alkoxy”, and other substituents including “alkyl”part used herein may include all linear or branched types. Further, thealkyl, alkoxy, and hydroxyalkyl according to the present inventionpreferably have 1 to 7 carbon atoms in a linear form or a linear formwith 1 to 7 carbon atoms, but an alkyl, alkoxy and hydroxyalkyl having 8to 30 carbon atoms may also be an embodiment of the present invention.

Further, “alkenyl” used herein is a linear or branched hydrocarbonincluding one or more double bonds. For example, the alkenyl may beethenyl, prop-1-en-1-yl, prop-1-en-2-yl, prop-2-en-1-yl, prop-2-en-2-yl,but-1-en-1-yl, but-1-en-2-yl, 2-methyl-prop-1-en-1-yl, but-2-en-1-yl,but-2-en-2-yl, buta-1,3-dien-1-yl, buta-1,3-dien-2-yl, and the like, butis not limited thereto. The term “alkynyl” used herein is a linear orbranched hydrocarbon including one or more triple bonds. For example,the alkynyl may be ethynyl, prop-1-yn-1-yl, prop-2-yn-1-yl,but-1-yn-1-yl, but-1-yn-3-yl, but-3-yn-1-yl, and the like, but is notlimited thereto.

In addition, the composition according to an embodiment of the presentinvention may promote skin lipid biosynthesis by containing the compoundas an active ingredient. In detail, according to the present invention,the differentiation of skin keratinocytes is promoted to restore skinbarrier function and to overcome skin pulling and roughness.

In other words, the composition according to an embodiment of thepresent invention is preferably an anti-inflammatory composition, andmay also be effectively useful as a composition for skin moisturizing,skin keratinocyte differentiation promotion, and/or skin barrierfunction recovery.

The compound according to an embodiment of the present invention is avery stable material and is easy to formulate. Preferably, R₁ may be(C1-C20)alkyl, (C1-C20)alkoxy, or hydroxy(C1-C20)alkyl having a linearform particularly from the viewpoint of exhibiting the anti-inflammatoryeffect effective for atopic dermatitis, allergic dermatitis, or thelike.

Further, in the anti-inflammatory composition according to an embodimentof the present invention, R₁ and R₂ may be each independently ethyl,n-propyl, n-butyl, or n-pentyl from the viewpoint of having excellentsolubility and compatibility with a solvent.

In the anti-inflammatory composition according to an embodiment of thepresent invention, from the viewpoint of having excellent solubility andcompatibility with a solvent, being safe in a living body, and having ananti-inflammatory effect, preferably, R₃ of the compound may be selectedfrom the following structures:

in structures above,

R₂₁ and R₂₂ are each independently hydrogen or (C1-C7)alkyl.

In the anti-inflammatory composition according to an embodiment of thepresent invention, it is preferable that R₂₁ and R₂₂ of the compound areeach independently selected from methyl, ethyl, and propyl, but are notlimited thereto.

The compound according to an embodiment of the present invention is avery stable substance and is easy to formulate. Particularly, from theviewpoint of exhibiting the anti-inflammatory effect effective foratopic dermatitis, allergic dermatitis, or the like, more preferably, R₃of the compound may be a hydroxy(C3-C4)alkyl in a branched form, and asa more preferred example, may be a compound represented by ChemicalFormula 2 below, but is not limited thereto.

in Chemical Formula 2,

R₁ is hydrogen, (C1-C7)alkyl or hydroxy(C1-C7)alkyl, and

R₂ is (C1-C7)alkyl or hydroxy(C1-C7)alkyl.

Further, the present applicant also found that the anti-inflammatorycomposition including the compound represented by Chemical Formula 1 asan active ingredient may be formulated into a cosmetic composition, apharmaceutical composition, and the like. An amount range of thecompound may be appropriately adjusted according to requirements such asinhibition of cytokine activity, skin safety, easiness of formulation,and the like. In the cosmetic composition and/or the pharmaceuticalcomposition, the amount range of the active ingredient is not limited,but may be 0.001 to 50 wt %, preferably 0.01 to 30.0 wt %, and morepreferably 0.01 to 20.0 wt % based on the total weight of thecomposition.

Hereinafter, the anti-inflammatory cosmetic composition according to anembodiment of the present invention is described in detail.

The cosmetic composition according to the present invention may beprepared by including suitable additives conventionally used. Here,examples of the additive may include one or more selected from one ormore aqueous additives selected from purified water, stabilizers,emulsifiers, thickeners, moisturizers, liquid crystal membranestrengthening agents, pH regulators, antibacterial agents, water-solublepolymers, coating agents, metal ion sequestering agents, amino acids,organic amines, polymer emulsions, pH adjusters, skin nutrients,antioxidants, antioxidant aids, preservatives, flavoring, and the like;and one or more oil additives selected from oils, waxes, hydrocarbonoils, higher fatty acid oils, higher alcohols, synthetic ester oils,silicone oils, and the like.

The aqueous additive according to an embodiment of the present inventionis not limited as long as it is a raw material generally used in theart. Specific examples may include glycerin, dipropylene glycol,butyleneglycol, pentylene glycol, methylpropanediol, sorbitol,diglycerin, erythritol, pentaerythritol, polybutylene glycol-10,polyglycerin-3, polyglycerin-4, polyglycerin-6, polyglycerin-10,polyglycerin-20, polyglycerin-40, sorbes-5, sorbes-6, sorbes-20,sorbes-30, sorbes-40, inositol, maltitol, maltose, mannan, mannitol,mannose, lactitol, lactose, dihydroxypropyl PG-glucoside,dithiaoctanediol, fructose, glucamine, methylglucamine, glucose,1,2,6-hexanethiol, methyl gluceth-10, methyl gluceth-20, ozonizedglycerin, phytantriol, thioglycerin, threitol, trimethylolpropane,xylitol, EDTA, guar gum, quince seed, carrageenan, galactan, gum arabic,pectin, mannan, starch, xanthan gum, curdlan, methylcellulose, hydroxylethylcellulose, carboxymethyl cellulose, methyl hydroxypropylcellulose,chondroitin sulfate, dermatan sulfate, glycogen, heparan sulfate,hyaluronic acid, sodium hyaluronate, tragacanth gum, keratan sulfate,chondroitin, mucoitin sulfate, hydroxyethyl guar gum, carboxymethyl guargum, dextran, keratosulfuric acid, locust bean gum, succinoglucan,charonin acid, chitin, chitosan, carboxymethyl chitin, agar, polyvinylalcohol, polyvinyl pyrrolidone, carboxyvinyl polymer, sodiumpolyacrylate, polyethylene glycol, bentonite, methyl paraben, propylparaben, phenoxyethanol, 1,2-hexanediol, ethylhexyl glycerin, and thelike. Further, the oil additive is not limited as long as it is a rawmaterial generally used in the art, and may include, for example, liquidoils such as olive oil, camellia oil, jojoba oil, triglyceride,trioctanoic acid glycerin, triisopalmitic acid glycerin, and the like,solid oils such as palm oil, hardened palm oil, palm oil, hardened oil,and hardened castor oil, and the like, beeswax, candelilla wax, carnaubawax, lanolin, jojoba wax, and the like. Examples of the hydrocarbon oilmay include liquid paraffin, squalane, petrolatum, microcrystalline wax,and the like. Examples of the higher fatty acid may include waxes suchas lauric acid, myristic acid, palmitic acid, stearic acid, behenicacid, and the like, cetyl alcohol, stearyl alcohol, behenyl alcohol,myristyl alcohol, cetostearyl alcohol, and the like. Examples of thesynthetic ester oil may include higher alcohols such as isopropylmyristate, cetyl octanoate, octyldodecyl myristate, isopropyl palmitate,hexyl laurate, myristyl myristate, cetyl lactate, isocetyl isostearate,neopentyl glycol dicaprate, ethylhexyl glycerin, cetyl ethyl hexanoate,ethylhexyl palmitate, cetostearyl alcohol, and the like, chain typesilicone oils such as dimethylpolysiloxane, methylphenylpolysiloxane,methylhydrogenpolysiloxane, and the like, cyclic silicone oils such asdodecamethylcyclohexasiloxane, octamethylcyclotetrasiloxane,decamethylcyclopentasiloxane, and the like, but the synthetic ester oilis not limited thereto.

The cosmetic composition according to an embodiment of the presentinvention may be prepared in the form of a general emulsifiedformulation, a solubilized formulation, and the like, by using aconventionally known preparation method in addition to the preparationmethod specifically disclosed in the present invention. Here, thecosmetic composition may be appropriately selected according to thepurpose. As a specific example, the cosmetic composition may beformulated into a formulation selected from the group consisting ofsoftening toner, astringent toner, nutritional toner, eye cream,nutritional cream, massage cream, cleansing cream, cleansing foam,cleansing water, powder, essence, and a pack, but is not limitedthereto.

Hereinafter, the anti-inflammatory pharmaceutical composition accordingto an embodiment of the present invention is described in detail.

The anti-inflammatory pharmaceutical composition according to anembodiment of the present invention may include a pharmaceuticallyacceptable carrier according to a method that may be easily performed bya person skilled in the art to which the present invention belongs. Thepharmaceutically acceptable carrier to be included in theanti-inflammatory pharmaceutical composition is conventionally used inthe preparation, and may be lactose, dextrose, sucrose, sorbitol,mannitol, starch, acacia rubber, calcium phosphate, alginate, gelatin,calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone,cellulose, water, syrup, methyl cellulose, methyl hydroxybenzoate,propyl hydroxybenzoate, talc, magnesium stearate, or mineral oil, but isnot limited thereto. The anti-aging pharmaceutical composition of thepresent invention may further include a lubricant, a wetting agent, asweetener, a flavor, an emulsifier, a suspension, a preservative, or thelike, in addition to the above-described components.

The pharmaceutical composition according to an embodiment of the presentinvention may be prepared by using a conventionally known preparationmethod in addition to the preparation method specifically disclosed inthe present invention, and may be formulated in an appropriate formaccording to the purpose. Specific examples thereof may include theforms of, but are not limited to, lotion, ointment, gel, cream, a patch,spray, and the like.

The anti-inflammatory composition according to an embodiment of thepresent invention has an inflammatory skin disease-improving effect. Inparticular, the effect of improving atopic dermatitis and/or allergicdermatitis is excellent.

Hereinafter, preferred embodiments of the present invention aredescribed to assist in understanding the present invention. However, thefollowing Examples are provided only for the purpose of easierunderstanding of the present invention, and the Examples below aremerely illustrative and not intended to limit the scope of the presentinvention in any way.

(Evaluation Method)

1. Confirmation of Cytotoxicity

The cell viability for human fibroblast (ATCC 2076) was measured usingthe anti-inflammatory composition prepared in the following Examples.

The human fibroblast (ATCC 2076) with a concentration of 5×10⁴ cells/mlwas inoculated into a 24-well culture plate of Iscove's ModifiedDulbecco's Medium (IMDM, GIBCO) containing 10% bovine serum. After 24hours of inoculation, the medium was replaced with a serum-free medium,and the test sample was added at a concentration of 0.5, 1, 5 or 10μg/ml and incubated in a 5% CO₂ incubator at 37° C. for one day. Then,the supernatant was removed, the cells were washed with 200 μl of 5%phosphate buffered saline (PBS), 1.0 ml of MTT solution was added toeach well, and after 4 hours, and the MTT was removed. Next, 1.0 ml ofDMSO was added to each well, and incubation was performed overnight at37° C. The absorbance at 570 nm was measured to determine the cellviability using Equation 1 below, and results thereof are shown in Table1 below. Here, as a negative control group, a test group in which theactive ingredient was not used was adopted.Cell viability (%)=(A _(570λvalue) /B _(570λvalue))×100  [Equation 1]

A: Absorbance value at 570 nm of Example

B: Absorbance value at 570 nm of negative control group

2. Confirmation of Safety on Human Skin

In order to induce skin irritation, 0.1 wt % of sodium lauryl sulfate(SLS) was used as a positive control. Whether or not theanti-inflammatory composition according to the present inventionstimulates the skin was measured by preparing formulations in whichrespective active ingredients prepared in the following Examples wereadded in amounts of 0.1, 0.05, and 0.01 wt %, and adhering, for a totalof 9 times, 24-hour cumulative patches every other day on the upperforearm in 30 healthy adults using the prepared formulations. A finnchamber (Epitest Ltd, Finland) was used for the patch test, and 15 μl ofeach of the above-prepared external preparations for skin was addeddropwise to the chamber, and the patch was applied. A skin reactivitywas confirmed by scoring the degree of skin reaction on each skin usingthe following Equation 2, and results thereof are shown in Table 2below. Here, a safe composition is judged when the average skinreactivity is less than 3.Average skin reactivity=[{Σ(reaction index (a)×number of subjectsshowing reaction (b))}/(total number of subjects×highest score (4points))×100]=number of tests  [Equation 2]

Reaction index: No visible reaction (0), slight erythema (1), strongerythema (2), strong erythema and edema (3), strong erythema, swelling,and vesicle (4)

3. Measurement of Anti-Inflammatory Effect

In order to measure the anti-inflammatory efficacy, atopic dermatitiswas induced with respect to IL-8 and IL-17A, which areinflammation-inducing cytokines, and expression amounts thereof weremeasured.

In order to induce atopic dermatitis, the 3D culture tissue (EpiDermFull Thickness 400, sold by MatTek) media containing Poly (I:C), TNF-α,IL-4 and IL-13 were used, and treated for 72 hours withN-(2-hydroxyethyl)octanamide at a final concentration of 100 μM. Then,the 3D culture tissue was immobilized on formalin to make a paraffinblock, and the degree of expression of inflammation-inducing cytokinewas evaluated. Results thereof are shown in FIGS. 1 and 2.

4. Measurement of Atopic Dermatitis Improvement Effect

In order to measure atopic dermatitis improvement effect, theanti-inflammatory compositions were prepared according to the followingExamples. Here, the atopic dermatitis improvement effect was measuredusing an eczema area severity index (EASI) score. 30 pediatric patientswith atopic dermatitis were treated twice a day for 4 weeks, and theneffects on atopic symptoms were measured. Here, as a negative controlgroup, a test group in which the active ingredient was not used wasadopted.

Example 1

Step 1.

2-Ethylhexanoic acid (1.9 mmol),1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (2.8 mmol)and 1-hydroxybenzotriazole hydrate (2.8 mmol) were well stirred indichloromethane (6 ml) and methanol (0.2 ml). Serinol (2.1 mmol) wasadded, triethylamine (5.7 mmol) was slowly added dropwise, and themixture was stirred for 5 hours or more. Water was added to the reactionmixture, and the reaction mixture was extracted with dichloromethane.The organic phase was dried over MgSO₄ and distilled under reducedpressure. The crude product was purified by silica gel chromatography(dichloromethane:methanol=20:1) to obtain the final desired compoundN-(1,3-dihydroxypropan-2-yl)-2-ethylhexanamide (Yield: 23.5%).

MS (ESI pos, ion) m/z 218 (MH⁺), 240 (M+Na), C11H23NO3, Exact masscalculated: 217.17

¹H-NMR (600 MHz, DMSO): 7.42-7.41 (d, 1H), 4.56-4.54 (m, 2H), 3.77-3.72(m, 1H), 3.42-3.36 (m, 4H), 2.08-2.04 (m, 1H), 1.46-1.38 (m, 2H),1.34-1.13 (m, 6H), 0.83 (t, 3H), 0.78 (t, 3H)

Step 2.

An anti-inflammatory composition containing 1.0 wt % (in H₂O) ofN-(1,3-dihydroxypropan-2-yl)-2-ethylhexanamide prepared in step 1 abovewas prepared.

The anti-inflammatory composition prepared by the above-described methodshowed no cytotoxicity in the concentration range of the evaluationmethod described above (see Table 1). In addition, as a result ofconfirming safety on human skin, it could be confirmed that the averageskin reactivity was 0.93 (when 0.1 wt % of the composition was used),and thus the composition was very safe on the skin (see Table 2).

In FIG. 1, AD represents a skin model in which atopic dermatitis wasinduced, and the anti-inflammatory effect was evaluated based on theexpression amounts of IL-8 and IL-17A.

As a result, it was confirmed that by treating the anti-inflammatorycomposition according to the present invention with the skin model inwhich atopic dermatitis was induced, IL-8 and IL-17A expression amountscould be implemented at a similar level to that of normal skin model,which is the control, and thus it was confirmed that the composition ofthe present invention showed an excellent effect on atopic dermatitis.

Further, the inhibitory effect of each cytokine was quantified based onthe results obtained through the immunohistochemistry obtained in FIG.1, and shown in FIG. 2.

As a result, it was confirmed that the anti-inflammatory compositionaccording to the present invention showed not only IL-8 inhibitoryeffect by 48.5% or more but also IL-17A inhibitory effect by 58.9% ormore as compared with the skin model in which atopic dermatitis wasinduced.

Further, it was confirmed that as a result of measuring the atopicdermatitis improvement effect, a significant numerical decrease wasexhibited.

Example 2

Step 1.

2-Hexyloctanoic acid (0.44 mmol),1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.66 mmol),and 1-hydroxybenzotriazole hydrate (0.66 mmol) were well stirred indichloromethane. L-tyrosine methyl ester hydrochloride (0.48 mmol) wasadded, triethylamine (1.3 mmol) was slowly added dropwise, and themixture was stirred for 5 hours or more. Water was added to the reactionmixture, and the reaction mixture was extracted with dichloromethane.The organic phase was dried over MgSO₄ and distilled under reducedpressure. The crude product was purified by silica gel chromatography(dichloromethane:methanol=50:1) to obtain the final desired compoundmethyl(2-hexyloctanoyl)-L-tyrosinate (Yield: 43.1%).

MS (ESI pos, ion) m/z 406 (MH⁺), 428 (M+Na), C24H39NO4, Exact masscalculated: 405.29

¹H-NMR (600 MHz, CDCl3): 6.99-6.97 (d, 2H), 6.74-6.72 (m, 2H), 5.84-5.82(d, 1H), 5.23 (s, 1H), 4.93-4.90 (m, 1H), 3.73 (s, 3H), 3.09-2.99 (m,2H), 2.02-1.97 (m, 1H), 1.55-1.49 (m, 2H), 1.39-1.33 (m, 2H), 1.29-1.11(m, 16H), 0.89-0.86 (m, 6H)

Step 2.

An anti-inflammatory composition containing 1.0 wt % (in H₂O) of methyl(2-hexyloctanoyl)-L-tyrosinate prepared in step 1 above was prepared.

TABLE 1 Used amount (μM) Cell viability (%) Example 1 250 108% 50 101%10 101% 2 101% 0.4  98% 0.08 100% 0.016  99% 0.0032 106% 0.00064 110%Negative control — 100% group

According to the results shown in Table 1 above, no significantcytotoxic effect was observed when compared with the test group(negative control group) in which the active ingredient was not usedeven after treatment up to 250 uM concentration.

TABLE 2 Skin average Used amount (wt %) reactivity Example 1 0.1 0.930.05 0.46 0.001 0.28 Control group 0.1 4.17

According to the results shown in Table 2 above, no significant skinirritation was observed even after treatment up to the concentration of0.1 wt %, and it could be determined that the composition had veryexcellent stability compared to the positive control group treated withSLS.

Thus, the anti-inflammatory composition according to the presentinvention is expected to be useful for various types of inflammatoryskin diseases since the composition has excellent inhibitory effect onthe expression of inflammatory skin disease-related mediating factor.

Although specific embodiments of the present invention are described indetail, it will be apparent to those skilled in the art that thespecific description is merely an embodiment and should not be construedas limiting the scope of the present invention. Therefore, thesubstantial scope of the present invention is defined by theaccompanying claims and equivalent thereof.

The invention claimed is:
 1. A method of treating an atopic dermatitisin a subject in need of such treatment, the method comprising:administering a composition to the subject in an amount effective toinhibit expression of IL-8 or IL-17, wherein the composition comprises acompound represented by Chemical Formula 1:

wherein R₁ is hydrogen or C1-C7 alkyl; wherein R₂ is C1-C7 alkyl; andwherein R₃ is

wherein R₁₁ is hydroxy C1-C7 alkyl and R21 is hydrogen or C1-C7 alkyl.2. The method of claim 1, wherein the compound is represented byChemical Formula 2:

wherein R₁ is hydrogen or C1-C7 alkyl.
 3. The method of claim 1, whereinthe compound has an amount of 0.001 to 50 wt % based on the total weightof the composition.
 4. The method of claim 1, wherein administering thecomposition comprises topically administering the composition onto askin of the subject.
 5. The method of claim 4, wherein the compositionis formulated as softening toner, astringent toner, nutrition toner, eyecream, nutrition cream, massage cream, cleansing cream, cleansing foam,cleansing water, powder, essence, or a pack.
 6. The method of claim 4,wherein the composition is formulated as lotion, ointment, gel, cream, apatch, or spray.
 7. The method of claim 1, wherein R₃ is

and R₁₁ is hydroxy C1-C7 alkyl.
 8. The method of claim 7, wherein R₁₁ ishydroxy-C3-alkyl.